The present invention is directed to mammographic techniques, particularly to an x-ray source used in screening mammography techniques, and more particularly to an improved x-ray source which produces a higher energy x-ray spectrum which enables mammographic screening breasts with higher than average x-ray opacity without increasing the radiation dose.
Breast cancer, which will eventually strike one out of every nine women in the United State, is a major and growing national health problem. Despite decades of research, the mortality rate for this disease remains high, and its causes are unknown. About 175,000 American women will contract the disease this year, and 45,000 will die of breast cancer (about one person every 12 minutes). For women aged 35 to 50, cancer is the leading cause of death, and breast cancer is the most common malignancy. In addition, the incidence of new breast cancer cases diagnosed in the United States is increasing by about 1.8% each year even when corrected for the general aging of the female population.
Treatment for advanced breast cancer can involve surgery that is disfiguring, relatively high doses of radiation, and potentially toxic drugs with unpleasant side effects. Women undergoing treatment often suffer baldness and early menopause. Even the safety of silicone implants that have been used in breast reconstruction is now in doubt.
On the positive side, survival rates are slowly creeping upwards. Twenty years ago, 68% of women with breast cancer were alive five years after surgery. Today, the five-year survival rate is 77%. Early detection through screening is the most important factor in this improvement, and many studies during the last twenty years have shown that early detection can lead to a high probability of a cure.
By the time breast cancer reaches a size that can be felt as a lump, it has been growing for an average of ten years. The most effective way to detect breast cancer at an early stage is by a physical examination combined with breast x-ray imaging, or mammography. Indeed, mammography is the only means of detecting the microcalcifications that often accompany small, non palpable breast cancers (those that cannot be felt).
Microcalcifications are small grains of calcium-rich mineral deposits in breast tissue. In an estimated 30 to 50% of cases, microcalcifications seen on a mammogram are the first clue to early breast cancer. Up to 80% of breast cancers have associated microcalcifications that can be verified under a microscope. Microcalcifications associated with malignancy are generally less thaw 500 .mu.m in size. Because the mineral deposits absorb x-rays slightly more strongly than do surrounding soft tissues, they are visible in a transmission x-ray image on conventional film at an earlier stage than are soft-tissue masses.
As it is presently practiced, mammography does not detect all breast cancers. Many mineral deposits are faint and subtle on conventional x-ray film., and rather than having distinct edges, they fade gradually into the surroundings. Thus, they can be quite difficult to locate. The potential for oversight is large even when screening is done by the most experienced radiologists.
When directly viewing traditional x-ray film on a light box, a mammographer must systematically search the entire image--by literally using a magnifying glass--to detect all potentially important microcalcifications. Obviously, this type of screening work requires a highly trained (and highly paid) individual. Medical center radiologists estimate that as many as 80% of all women have some calcifications in their breasts. Even though most breasts exhibit some degree of calcification, the presence of deposits alone does not necessarily mean cancer. The size, shape, and distribution of clustered deposits determine whether they represent an indicator for breast cancer in an individual.
In addition, the breast contains many other complex structures that exhibit radiographic contrast, and scratches or spots on the x-ray film can mimic the appearance of microcalcifications. All these factors contribute to the problem of differentiating trouble spots from false alarms. For example, normal breast connective tissue forms linear features in an x-ray image. When two or more such features cross in the image, they may appear as a white spot on film.
Compounding the difficulty of visually spotting significant microcalcifications is the speed at which expert mammographers reach a decision regarding malignancy. At one prominent mammography clinic, 30,000 cases are screened each year, and some radiologists scan up to 300 film records in a single day. The American Cancer Society recommends that a woman between the ages of 40 and 49 have a mammogram every two years and that she do so annually thereafter. If every female in the United States followed this recommendation, 170 million new images would need to be screened each year.
Microcalcifications are often present for reasons other than cancer. However, if the pattern of calcification in an individual is suspicious, then biopsy may be warranted. A biopsy usually means surgical removal of the tissue and subsequent examination under a microscope. Of those women undergoing biopsy as a result of a suspicious mammogram, about one in five have breast cancer.
Using transitional x-ray film screening techniques, which do not apply quantitative criteria, varying interpretations are inevitable, and the miss rate today is fairly high. Indeed, one recent analysis of 320 cases of breast cancer in a screened population revealed 77 cancers (24%) that were missed by screening mammography. In this recent analysis, "missed" is taken to mean that retrospectively, an earlier mammogram revealed a structure or cluster of microcalcifications that are of medical significance. It is common for a breast cancer to be discovered by manual examination even though a mammogram within the preceding year or two has been judged to be negative. In the above-referenced analysis, 19 of the 77 missed cancers (25%) were found by means other than mammography. As it is presently practiced, interpreting mammograms is an exceedingly difficult art.
Most mammograms are obtained with a machine marketed specifically for mammography. Because of the small size and subtle contrast of breast microcalcifications, mammography requires the highest spatial and contrast resolution of any medical x-ray imaging procedure; that is, it requires the best possible image quality. Mammography is also essentially the only medical x-ray imaging procedure routinely done today on a screening basis; thus, it is imperative to use the lowest possible radiation dose.
By looking at the design of the machine itself, including the x-ray source, the required x-ray dose, and the time and money spent on manually interpreting mammograms, there are many areas in need of improvement. Also, given the choice between direct viewing of a film image by a human interpreter (in this case, a mammographer) and quantitative data presentation via computer, there is no natural or logical advantage to direct viewing. In fact, the opposite case can be made. The relation between optical density and the actual object itself is exceedingly complex. Many important physical factors, such as a polychromatic x-ray source, attenuation of photons, statistical noise in the image, and nonlinear optical density in the film, to name only a few, come into play in mammography.
In addition to these physics issues, human physiology and perception must be considered when a human directly interprets a film image. The eye's response to light passing through a film image depends on the observer, making many interpretations and diagnoses subjective. It has been known for decades that the eye and brain are rather good at spotting patterns, especially edges. However, the neural visual system is not very adept at discerning smooth gradients in optical density (discriminating between various shades of gray) or a comparing regions separated in space. This is to say nothing of fatigue, distractions, and other factors that come into play when a mammographer must scan and interpret scores or hundreds of images during a busy day. Even for objects located in adjacent regions, digitizers can measure density differences ten time smaller than those discernible to the unaided eye. In the final analysis, by providing an improved x-ray source, digitizing the data, using a computer to help identify salient features, and then presenting results in creative ways, many features of a film image can be more clearly conveyed.
The x-ray source in conventional mammography typically uses a molybdenum target and filter. Molybdenum (Mo) was selected for largely historical reasons during the development of x-ray tubes, because it is a robust anode material, and because it yields high contrast when used with film. An x-ray generator with an anode made of Mo (often containing some alloying material for longer operating life) produces a relatively low-energy x-ray spectrum that is rich in the Mo characteristic lines at about 17.5 keV and 19.6 keV. This spectrum works well for breasts that are relatively transparent to x-rays, but requires administering sharply increasing radiation doses in order to image breasts with higher than average x-ray opacity, thereby increasing the risk of induced breast cancer via radiation doses for mammograms.
Recently, studies have been made to determine the optimal x-ray energy for mammography, and it was determined that the optimal energy depends not only on the size and composition of the defect to be imaged (such as a large, dense mass versus a small microcalcification), but also on the size and composition of the breast under examination. These studies involved three sizes of breasts: 1) Thin breasts (compressed to 2 cm during imaging), 2) average breasts (5 cm), and 3) thick breasts (8 cm), with all breasts being of average composition (50% adipose and 50% gland). In general, it was found that to image a 100 .mu.m calcification in thin breasts (compressed to 2 cm) the energy was low and the 17.5 keV was sufficient, but if an energy of about 17.5 keV was used to image a 100 .mu.m flaw in a thick breast (compressed to 8 cm), then the radiation dose required was 100 times the dose required in a 2 cm (thin) breast. For average breasts and especially thick, glandular breasts, the desired x-ray energy approached 25 keV. These studies demonstrate that this energy region (25 keV) is also appropriate for imaging a larger 2 mm mass. Such results suggest that the x-ray sources considered best practice today (ones using molybdenum, which emits strongly at 17.5 keV) are poorly suited for mammography. In fact, for the full range of breast-imaging tasks, a source rich in 22 to 25 keV photons is needed.
The present invention satisfies this need by providing an x-ray source or generator, wherein the x-ray spectrum could be adjusted to be rich in the 20 to 35 keV region by the choice of anode material, filtering, and voltage applied to the generator. It has been recognized that by using anode material, such as silver, rhodium, and tungsten, for example, screening mammography can be carried out using low radiation doses regardless of the size and/or composition of the breast being examined, thereby reducing the risk of induced breast cancer.